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Geerling, J.J. (author), Boon, M.R. (author), van der Zon, G.C. (author), van den Berg, S.A.A. (author), van den Hoek, A.M. (author), Lombès, M. (author), Princen, H.M.G. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), Guigas, B. (author)
Metformin is the first-line drug for the treatment of type 2 diabetes. Besides its well-characterized antihyperglycemic properties, metformin also lowers plasma VLDL triglyceride (TG). In this study, we investigated the underlying mechanisms in APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism. We found that...
article 2014
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Voshol, P.J. (author), Rensen, P.C.N. (author), van Dijk, K.W. (author), Romijn, J.A. (author), Havekes, L.M. (author), TNO Kwaliteit van Leven (author)
The obesity epidemic is associated with an increased incidence of type 2 diabetes, cardiovascular morbidity and various types of cancer. A better insight into the molecular mechanisms that underlie adipogenesis and obesity may result in novel therapeutic handles to fight obesity and these associated diseases. Adipogenesis is determined by the...
article 2009
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Delsing, D.J.M. (author), Offerman, E.H. (author), van Duyvenvoorde, W. (author), van der Boom, H. (author), de Wit, E.C.M. (author), Gijbels, M.J.J. (author), van der Laarse, A. (author), Jukema, J.W. (author), Havekes, L.M. (author), Princen, H.M.G. (author), Gaubius Instituut TNO (author)
Background - The present study investigated whether the ACAT inhibitor avasimibe can reduce atherogenesis independently of its cholesterol-lowering effect in ApoE*3-Leiden mice. Methods and Results - Two groups of 15 female ApoE*3-Leiden mice were put on a high-cholesterol (HC) diet; 1 group received 0.01% (wt/wt) avasimibe mixed into the diet....
article 2001
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de Haan, W. (author), de Vries-van der Weij, J. (author), Mol, I.M. (author), Hoekstra, M. (author), Romijn, J.A. (author), Jukema, J.W. (author), Havekes, L.M. (author), Princen, H.M.G. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)
Pregnane X receptor (PXR) agonism has been shown to affect multiple steps in both the synthesis and catabolism of HDL, but its integrated effect on HDL metabolism in vivo remains unclear. The aim of this study was to evaluate the net effect of PXR agonism on HDL metabolism in ApoE*3-Leiden (E3L) and E3L.CETP mice, well-established models for...
article 2009
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Havekes, L. (author), Vermeer, B.J. (author), de Wit, E. (author), Gaubius instituut TNO (author)
The suppression of cellular cholesterol synthesis by low density lipoprotein (LDL) from a normal and from a homozygous familial hypercholesterolemic subject was measured on normal fibroblasts and on fibroblasts derived from the same homozygous familial hypercholesterolemic patient. On normal fibroblasts both LDL preparations (density 1.019 to 1...
article 1980
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de Roos, B. (author), Duivenvoorden, I. (author), Rucklidge, G. (author), Reid, M. (author), Ross, K. (author), Lamers, R.J.A.N. (author), Voshol, P.J. (author), Havekes, L.M. (author), Teusink, B. (author), TNO Kwaliteit van Leven (author)
article 2005
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de Beer, F. (author), Hendriks, W.L. (author), van Vark, L.C. (author), Kamerling, S.W.A. (author), van Dijk, K.W. (author), Hofker, M.H. (author), Smelt, A.H.M. (author), Havekes, L.M. (author), Gaubius instituut TNO (author)
The binding of β-VLDL to heparan sulfate proteoglycans (HSPG) has been reported to be stimulated by both apoE and lipoprotein lipase (LPL). In the present study we investigated the effect of the isoform and the amount of apoE per particle, as well as the role of LPL on the binding of β-VLDL to HSPG. Therefore, we isolated β-VLDL from transgenic...
article 1999
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Hoffer, M.J.V. (author), Bredie, S.J.H. (author), Boomsma, D.I. (author), Reymer, P.W.A. (author), Kastelein, J.J.P. (author), de Knijff, P. (author), Demacker, P.N.M. (author), Stalenhoef, A.F.H. (author), Havekes, L.M. (author), Frants, R.R. (author), Gaubius Instituut TNO (author)
Familial combined hyperlipidaemia (FCHL) is one of the major genetic causes of coronary heart disease (CHD) and is characterised by elevated levels of plasma cholesterol and/or triglycerides in individuals within a single family. Decreased lipoprotein lipase (LPL) activity has been found in some cases of FCHL. A recent study revealed a common...
article 1996
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Lansink, M. (author), Jong, M. (author), Bijsterbosch, M. (author), Bekkers, M. (author), Toet, K. (author), Havekes, L. (author), Emeis, J. (author), Kooistra, T. (author), Gaubius instituut TNO (author)
Several clinical studies have demonstrated an inverse relationship between circulating levels of estrogen and tissue-type plasminogen activator (t-PA). The present study was designed to test the hypothesis that estrogen lower plasma levels of t-PA by increasing its clearance from the bloodstream. 17α-Ethinyl estradiol (EE) treatment resulted in...
article 1999
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Hu, L. (author), Bovenschen, N. (author), Havekes, L.M. (author), van Vlijmen, B.J.M. (author), Tamsma, J.T. (author), TNO Kwaliteit van Leven (author)
article 2007
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Hoffer, M.J.V. (author), Niththyananthan, S. (author), Naoumova, R.P. (author), Kibirige, M.S. (author), Frants, R.R. (author), Havekes, L.M. (author), Thompson, G.R. (author), Gaubius Instituut TNO (author)
Apolipoprotein E (apoE) is one of the major protein constituents of chylomicron and very low density lipoprotein (VLDL) remnants and plays a central role as a ligand in the receptor-mediated uptake of these particles by the liver. Here we describe a new variant of apoE, apoE1-Hammersmith, which is associated with dominantly expressed type III...
article 1996
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Koopmans, S.J. (author), Jong, M.C. (author), Que, I. (author), Dahlmans, V.E.H. (author), Pijl, H. (author), Radder, J.K. (author), Frölich, M. (author), Havekes, L.M. (author), Gaubius Instituut TNO (author)
Aims/hypothesis. Insulin resistance for glucose metabolism is associated with hyperlipidaemia and high blood pressure. In this study we investigated the effect of primary hyperlipidaemia on basal and insulin-mediated glucose and on non-esterified fatty acid (NEFA) metabolism and mean arterial pressure in hyperlipidaemic transgenic mice...
article 2001
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Gijbels, M.J.J. (author), van der Cammen, M. (author), van der Laan, L.J.W. (author), Emeis, J.J. (author), Havekes, L.M. (author), Hofker, M.H. (author), Kraal, G. (author), Gaubius instituut TNO (author)
Apolipoprotein E3-Leiden (APOE3-Leiden) transgenic mice develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. We have studied the progression and regression of atherosclerosis using immunohistochemistry. Female transgenic mice were fed a moderate fat diet to study atherosclerosis over a longer time period. Fatty...
article 1999
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van den Berg, S.A.A. (author), Heemskerk, M.M. (author), Geerling, J.J. (author), van Klinken, J.B. (author), Schaap, F.G. (author), Bijland, S. (author), Berbée, J.F.P. (author), van Harmelen, V.J.A. (author), Pronk, A.C.M. (author), Schreurs, M. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), van Dijk, K.W. (author)
Mutations in apolipoprotein A5 (APOA5) have been associated with hypertriglyceridemia in humans and mice. This has been attributed to a stimulating role for APOA5 in lipoprotein lipase-mediated triglyceride hydrolysis and hepatic clearance of lipoprotein remnant particles. However, because of the low APOA5 plasma abundance, we investigated an...
article 2013
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Groot, P.H.E. (author), van Vlijmen, B.J.M. (author), Benson, G.M. (author), Hofker, M.H. (author), Schiffelers, R. (author), Vidgeon-Hart, M. (author), Havekes, L.M. (author), Department of Vascular Biology, SmithKline Beecham Pharmaceuticals, Frythe, Welwyn, Hertfordshire, United Kingdom TNO-Prevention and Health, Gaubius Laboratory, Leiden, Netherlands SmithKline Beecham Pharmaceuticals, Frythe, Welwyn (Herts), AL6 9AR, United Kingdom TNO Preventie en Gezondheid (author)
Transgenic mice overexpressing the human dysfunctional apolipoprotein E variant, APOE*3 Leiden, develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. In the present study, we investigated the effects of diet composition and feeding period on serum cholesterol exposure and the amount of atherosclerosis in the aortic...
article 1996
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Parlevliet, E.T. (author), Heijboer, A.C. (author), Schroder-van der Elst, J.P. (author), Havekes, L.M. (author), Romijn, J.A. (author), Pijl, H. (author), Corssmit, E.P.M. (author), TNO Kwaliteit van Leven (author)
article 2008
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Post, S.M. (author), de Roos, B. (author), Vermeulen, M. (author), Afman, L. (author), Jong, M.C. (author), Dahlmans, V.E.H. (author), Havekes, L.M. (author), Stellaard, F. (author), Katan, M.B. (author), Princen, H.M.G. (author), Gaubius Instituut TNO (author)
Cafestol, a diterpene present in unfiltered coffee, potently increases serum cholesterol levels in humans. So far, no suitable animal model has been found to study the biochemical background of this effect. We determined the effect of cafestol on serum cholesterol and triglycerides in different mouse strains and subsequently studied its...
article 2000
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Mulder, M. (author), de Wit, E. (author), Havekes, L.M. (author), Gaubius Instituut TNO (author)
It has been suggested that besides the LDL-receptor, hepatocytes possess an apo E or remnant receptor. To evaluate which hepatic lipoprotein receptor is involved in VLDL remnant catabolism, we studied the binding of VLDL remnants to HepG2 cells. Native VLDL was obtained from type IIb hyperlipidemic patients and treated with bovine milk...
article 1991
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Geerling, J.J. (author), Wang, Y. (author), Havekes, L.M. (author), Romijn, J.A. (author), Rensen, P.C.N. (author)
Objective: Central neuropeptide Y (NPY) administration stimulates food intake in rodents. In addition, acute modulation of central NPY signaling increases hepatic production of very low-density lipoprotein (VLDL)-triglyceride (TG) in rats. As hypertriglyceridemia is an important risk factor for atherosclerosis, for which well-established mouse...
article 2013
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van Eck, M. (author), de Winther, M.P.J. (author), Herijgers, N. (author), Havekes, L.M. (author), Hofker, M.H. (author), Groot, P.H.E. (author), van Berkel, T.J.C. (author), Gaubius Instituut TNO (author)
In the arterial wall, scavenger receptor class A (SRA) is implicated in pathological lipid deposition. In contrast, in the liver, SRA is suggested to remove modified lipoproteins from the circulation, thereby protecting the body from their pathological action. The role of SRA on bone marrow-derived cells in lipid metabolism and atherogenesis was...
article 2000
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